Parched

August 13, 2019

Written by: Nitsan Goldstein

 

It’s been a hot and humid summer in Philly. Every morning by the time I get to lab, I feel like I could drink three bottles of water. How does my brain know that I need water? And how does it make me feel thirsty to make sure I stay hydrated? In this post we will explore the neural circuits that regulate thirst and drinking behavior.

 

Sensing water imbalance

The brain and body can sense when we are dehydrated by the makeup of our blood. If the overall volume of our blood is too small, or the concentration of proteins and cells in the blood (osmolarity) is too high, we need to drink water as well as retain the water we already have in order to maintain the right fluid balance, or homeostasis. In the brain, a group of regions collectively known as the lamina terminalis (LT) is essential for sensing these properties of circulating blood1. Normally, neurons themselves do not come into contact with the bloodstream due to the blood-brain-barrier. In this special region, however, the barrier is extremely thin. This allows these neurons exclusive access to the blood so that they can respond when there is an imbalance (Figure 1). The neurons also receive information regarding fluid homeostasis from circulating hormones such as Angiotensin II which is released by the liver and neural signals from the peripheral nervous system. This information converges in the LT to provide constant information about the body’s fluid needs. What happens, though, when these neurons sense that the body is dehydrated?

 

480px-Subfornical_organ_of_a_mouse
Figure 1. The subfornical organ. One region within the lamina terminalis is called the subfornical organ (the dark semicircle marked by the arrow). The structure hangs into a ventricle in the brain, which is the white area beneath the SFO. Ventricles are cavities where fluid circulates in and out of the brain. The proximity of the SFO to the ventricle along with many small capillaries surrounding it give the neurons in this region much more access to blood and circulating hormones that other neurons in the brain, and allows them to sense when there is a fluid imbalance in the body. Image by Tulemo and Wikimedia Commons.

 

Responding to water imbalance

When the body is dehydrated, the brain quickly prioritizes both the consumption of water and the retention of water already in the body. The LT orchestrates these distinct responses through various projections to other brain regions. For example, neurons projecting within the LT increase fluid intake while those projecting to another region, the hypothalamus, do not2. The region in the hypothalamus where they project, however, is known to alter blood pressure, heart rate, and kidney function. For example, the liver responds to dehydration by releasing hormones that signal the kidneys to absorb more salt from the blood, which increases water re-absorption and therefore blood volume and blood pressure. It has been suggested that these neurons coordinate such autonomic responses to dehydration, while the neurons projecting within the LT specifically affect behavior1.

If thirst is simply a reflection of blood volume and osmolarity, however, why does the first sip of water when you’re thirsty make you feel so much better so quickly? Why is cold water more satisfying than warm water? The answers to these questions are still under intense investigation, but work utilizing recent advances in technology has begun to uncover some answers. It seems that we have only scratched the surface of this sophisticated neural circuit.

 

Recent discoveries in thirst

Work in the last few years has dug deeper into the neural circuits regulating drinking behavior. One interesting study used mice to examine how neurons in the LT that stimulate drinking are inhibited once animals begin to drink3. They found that LT neurons are inhibited by two separate pathways. One pathway is activated when water is sensed in the mouth and throat. When drinking begins, this pathway rapidly inhibits the thirst-promoting neurons. The authors believe that this pathway is responsible for the perception that thirst is quenched so rapidly when we drink water, well before any changes in blood osmolarity are sensed. There is also evidence that this inhibition is stronger when cold liquids are sensed versus warm liquids2. In fact, even a cold sensation in the mouth has the ability to inhibit thirst-promoting neurons, potentially explaining why cold water is more satisfying than warm water when we are thirsty. Not surprisingly, the authors of this study also found that activating this pathway simultaneously activates the brain’s reward pathway. One sip of water, however, is not enough to restore fluid balance when the body is dehydrated. The activity of the thirst neurons, therefore, is also regulated by a separate pathway that responds to fluid sensing in the gut. This pathway, unlike that from the mouth and throat, does not affect the brain’s reward circuits (Figure 2).

thirst_circuits
Figure 2. Two pathways to inhibit thirst. When LT thirst neurons are active, they coordinate drinking behavior. When drinking begins, signals from the mouth and throat rapidly inhibit these thirst neurons (pathway 1). Eventually, signals from the body that actually reflect the current hydration state of the animal provide slower, longer lasting inhibition of these neurons (pathway 2). Figure created using BioRender.

The recently developed tools that were used in these studies will likely be used in the coming years to understand how the brain can tightly regulate this behavior that is so critical for survival. For example, it is well known that eating and drinking are closely linked. Eating increases thirst, and animals will not eat without access to water, even if they are hungry1. However, how the brain coordinates these two drives is not fully understood. Scientists hope to answer more questions like these to understand how the brain keeps us balanced.

 

 

 

 

References:

  1. Zimmerman, C. A., Leib, D.E., & Knight, Z.A. Neural circuits underlying thirst and fluid homeostasis. Rev. Neurosci. 18, 459-469 (2017).
  2. Zimmerman C.A., Lin, Y.C., Leib, D. E., Guo, L., Huey, E.L., Daly, G.E., Chen, Y., & Knight, Z.A. Thirst neurons anticipate the homeostatic consequences of eating and drinking. Nature 537, 680-684 (2016).
  3. Augustine, V. et al. Temporally and spatially distinct thirst satiation signals. Neuron 103, 242-249 (2019).

 

 

 

Images:

Cover Photo by Daria Shevtsova from Pexels

 

Figure 1 from Tulemo and Wikimedia Commons, CC BY-SA 4.0

commons.wikimedia.org/wiki/File:Subfornical_organ_of_a_mouse.jpg

 

Figure 2 created using BioRender

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